Continuing support is requested for the Yale Predoctoral Training Program in Human Genetics and Genomics. The program involves 44 trainers from 14 departments. The vast majority of trainers are primary and joint appointees in the Department of Genetics at the School of Medicine, and virtually all of the trainees over the last funding period have been matriculated in the Molecular, Cell Biology, Genetics &Development Track (MCGD) in Biological and Biomedical Sciences at Yale. The focus of the training proposed is the use of genetic and genomic approaches to understand human disease. The main methods used are positional cloning of human and mouse disease genes, complemented by bioinformatics and computational analysis, transgenic and knock-out methods in mouse as well as use of model organisms including Drosophila and C. elegans to define biochemical pathways and permit genetics screening for modifier loci. This integrated program bringing together faculty with diverse backgrounds and expertise provides a rich training environment for students. Admitted students have strong scientific backgrounds and research experience with high academic achievement. Training in the first year includes formal course work and research rotations, leading to selection of the thesis advisor's laboratory. In the second year students complete course work, and take a qualifying exam in which they must demonstrate mastery of genetics and defend two written research proposals. Subsequent years are devoted to dissertation research and preparation of the written thesis. In addition, students engage in supervised teaching experience. Support is requested for 7 graduate students per year for a five year period.